Microwave-assisted group-transfer cyclization of organotellurium compounds

Article abstract of DOI:10.1021/jo040155f

Primary- and secondary-alkyl aryl tellurides, prepared by arenetellurolate ring-opening of epoxides/O-allylation, were found to undergo rapid (3-10 min) group-transfer cyclization to afford tetrahydrofuran derivatives in 60-74% yield when heated in a microwave cavity at 250 °C in ethylene glycol or at 180 °C in water. To go to completion, similar transformations had previously required extended photolysis in refluxing benzene containing a substantial amount of hexabutylditin. The only drawback of the microwave-assisted process was the loss in diastereoselectivity which is a consequence of the higher reaction temperature. Substitution in the Te-aryl moiety of the secondary-alkyl aryl tellurides (4-OMe, 4-H, 4-CF₃) did not affect the outcome of the group-transfer reaction in ethylene glycol. However, at lower temperature, using water as a solvent, the CF₃ derivative failed to react. The microwave-assisted group-transfer cyclization was extended to benzylic but not to primary- and secondary-alkyl phenyl selenides.

Full text of DOI:10.1021/jo040155f

intermolecular addition could be efficiently effected using
fluorous tin hydride and short-time (5-10 min) micro-
wave irradiation followed by three-phase extraction in
the workup.3b We thought it would be interesting to study
the effect of microwave irradiation on atom- or group-
transfer reactions.3d In such processes, a carbon-centered
radical is initially produced by homolytic cleavage of a
C-X bond (where X is commonly halogen or a chalcogen
derivative).4 Following some type of radical transforma-
tion (for example, intra- or intermolecular addition), the
heteroatom is transferred from the radical precursor to
give the group- or atom-transfer product with regenera-
tion of the initially formed carbon-centered radical. In
contrast to products of reductive radical transformations,
the functional group of the radical precursor is retained
in the group-transfer product and is thus available for
further synthetic manipulations.
Micr ow a ve-Assisted Gr ou p -Tr a n sfer
Cycliza tion of Or ga n otellu r iu m
Com p ou n d s
Cecilia Ericsson and Lars Engman*
Uppsala University, Department of Chemistry, Organic
Chemistry, Box 599, SE-751 24 Uppsala, Sweden
lars.engman@kemi.uu.se
Received March 19, 2004
Abstr a ct: Primary- and secondary-alkyl aryl tellurides,
prepared by arenetellurolate ring-opening of epoxides/
O-allylation, were found to undergo rapid (3-10 min) group-
transfer cyclization to afford tetrahydrofuran derivatives in
60-74% yield when heated in a microwave cavity at 250 °C
in ethylene glycol or at 180 °C in water. To go to completion,
similar transformations had previously required extended
photolysis in refluxing benzene containing a substantial
amount of hexabutylditin. The only drawback of the micro-
wave-assisted process was the loss in diastereoselectivity
which is a consequence of the higher reaction temperature.
Substitution in the Te-aryl moiety of the secondary-alkyl aryl
tellurides (4-OMe, 4-H, 4-CF3) did not affect the outcome of
the group-transfer reaction in ethylene glycol. However, at
lower temperature, using water as a solvent, the CF3
derivative failed to react. The microwave-assisted group-
transfer cyclization was extended to benzylic but not to
primary- and secondary-alkyl phenyl selenides.
Concerning radical precursors for group-transfer chem-
istry, a comparative study of halogen and chalcogen
derivatives indicated similar rate constants for transfer
of elements/groups in the same row of the periodic table
(e.g., Br ≈ PhSe; I ≈ PhTe) and increased rates as one
traverses a column (e.g., PhTe is transferred ∼100 times
faster than PhSe).5
Since organotellurium compounds are often more
robust than iodides when carried through synthetic
sequences, substantial interest has focused to group-
transfer reactions of organotelluriums.6 So far, organo-
tellurium group-transfer chemistry has been successfully
applied for carbotelluration of alkynes,7 alkenes,8 iso-
nitriles,9 and quinones10 and for the decarbonylation of
aryltelluroformates.11 Initiation of the above processes
was brought about by various means. Often simple ther-
molysis or photolysis (or a combination of both) was suf-
ficient. In a rare case, thermolysis of azo-bis(isobutyroni-
trile) (AIBN) was used to get a chain-reaction going.7a
Microwave-assisted chemistry has much to offer syn-
thetic organic chemists.1 Although there is probably no
such phenomenon as a specific nonthermal “microwave
effect”, microwave dielectric heating causes an extremely
rapid and uniform energy transfer to the reactants of
chemical reactions. This will minimize formation of
byproducts/decomposition products and increase product
yields. In pressurized systems, it is possible to rapidly
increase the temperature far above the boiling point of
the solvent. Furthermore, the technique is energy ef-
ficient and the possibilities for applications in combina-
torial/parallel and automated chemistry and environ-
mental benign chemistry are obvious.2 Microwaves have
been recognized as an efficient means of heating organic
reactions since the mid-1980s. Since then, dramatic rate
accelerations have been demonstrated with a large
variety of organic reactions.1 Today, the number of
reports on microwave-assisted chemistry is well above
one thousand. However, surprisingly few reports have
appeared concerning microwave-assisted radical reac-
tions.3
(3) (a) Bose, A. K.; Manhas, M. S.; Ghosh, M.; Shah, M.; Raju, V.
S.; Bari, S. S.; Newaz, S. N.; Banik, B. K.; Chaudhary, A. G.; Barakat.
K. J . J . Org. Chem. 1991, 56, 6968. (b) Olofsson, K.; Kim, S.-Y.; Larhed,
M.; Curran, D. P.; Hallberg, A. J . Org. Chem. 1999, 64, 4539. (c)
Lamberto, M.; Corbett, D. F.; Kilburn, J . D. Tetrahedron Lett. 2003,
44, 1347. (d) For a recent example of microwave-assisted carboami-
noxylation, see: Wetter, C.; Studer, A. Chem. Commun. 2004, 174.
(4) For a review on group-transfer reactions, see: Byers, J . In
Radicals in Organic Synthesis, Volume 1: Basic Principles; Renaud,
P., Sibi, M., Eds.; Wiley-VCH Verlag GmbH: Weinheim, Germany,
2001; p 72.
(5) (a) Curran, D. P.; Martin-Esker, A. A.; Ko, S.-B.; Newcomb, M.
J . Org. Chem. 1993, 58, 4691. Xanthates, which were not included in
the study, have been shown by Zard to be excellently suited for group
transfer reactions under tin-free conditions. For reviews on the
chemistry of xanthates, see: (b) Zard, S. Z. Angew. Chem., Int. Ed.
Engl. 1997, 36, 672. Quiclet-Sire, B.; Zard, S. Z. Phosphorus Sulfur
Silicon 1999, 153-154, 137. (c) Zard, S. Z. In Radicals in Organic
Synthesis, Volume 1: Basic Principles; Renaud, P., Sibi, M., Eds.;
Wiley-VCH Verlag GmbH: Weinheim, Germany, 2001; p 90.
(6) As early as 1988, Barton and co-workers demonstrated that
organotelluriums are excellent accumulators and exchangers of carbon
centered radicals. Barton, D. H. R.; Ozbalik, N.; Sarma, C. Tetrahedron
Lett. 1988, 29, 6581.
Curran and Hallberg showed a few years ago that
hydrodebromination, reductive 5-exo-cyclization, and
(1) (a) Strauss, C. R.; Trainor, R. W. Aust. J . Chem. 1995, 48, 1665.
(b) Berlan, J . Radiat. Phys. Chem. 1995, 45, 581. (c) Caddick, S.
Tetrahedron 1995, 51, 10403. (d) Lidstro¨m, P.; Tierney, J .; Wathey,
B.; Westman, J . Tetrahedron 2001, 57, 9225. (e) Larhed, M.; Moberg,
C.; Hallberg, A. Acc. Chem. Res. 2002, 35, 717.
(2) (a) Larhed, M.; Hallberg, A. DDT 2001, 6, 406. (b) Wathey, B.;
Tierney, J .; Lidstro¨m, P.; Westman, J . DDT 2002, 7, 373. (c) Lew, A.;
Krutzik, P. O.; Hart, M. E.; Chamberlin, A. R. J . Comb. Chem. 2002,
4, 95.
(7) (a) Han, L.-B.; Ishihara, K.-I.; Kambe, N.; Ogawa, A.; Ryu, I.;
Sonoda, N. J . Am. Chem. Soc. 1992, 114, 7591. (b) Yamago, S.; Miyazoe,
H.; Yoshida, J . Tetrahedron Lett. 1999, 40, 2343. (c) Fujiwara, S.;
Shimizu, Y.; Shin-ike, T.; Kambe, N. Org. Lett. 2001, 3, 2085. (d)
Yamago, S.; Miyoshi, M.; Miyazoe, H.; Yoshida, J . Angew. Chem., Int.
Ed. 2002, 41, 1407.
10.1021/jo040155f CCC: $27.50 © 2004 American Chemical Society
Published on Web 06/29/2004
J . Org. Chem. 2004, 69, 5143-5146
5143

TABLE 1. Ar en etellu r ola te Rin g-Op en in g of Ep oxid es a n d O-Allyla tion
2-hydroxyalkyl aryl telluride,
2-allyloxyalkyl aryl telluride,
isolated yield (%)
entry
R1
R2
Ar
isolated yield (%)
1
2
3
4
5
6
7
-(CH2)4-
-(CH2)4-
-(CH2)4-
Bn
p-MeO-C6H4
Ph
p-CF3-C6H4
Ph
p-CF3-C6H4
Ph
Ph
1a , 89
1b, 98
1c, 82a
1d , 92
1e, 95
1f, 91
2a , 80
2b, 84
2c, 80a
2d , 81
2e, 80
2f, 72
-
H
H
H
H
Bn
PhOCH2
CH2dCH(CH2)2
1 g, 80a
a
From ref 12.
TABLE 2. In flu en ce of Ar yl Su bstitu en ts on Micr ow a ve-Assisted Gr ou p -Tr a n sfer Cycliza tion of Secon d a r y-Alk yl Ar yl
Tellu r id es 2
product, isolated yield (%),
entry
2-allyloxyalkyl aryl telluride
conditionsa
additive
reaction time (min)
endo/exo ratio
1
2
3
4
5
6
7
8
2a , Ar ) p-MeO-C6H4
2b, Ar) Ph
A
A
A
A
A
B
B
B
3
3
3a , 65, 1/1.1
3b, 69, 1/1.1
3b, 73, 1/1.1
3c, 67, 1/1.1
3c, 61, 1/1.1
3b, 72, 1/1.3
3b, 74, 1/1.3
3c, <10, 1/1.3
2b, Ar ) Ph
(ArTe)2 (0.5 equiv)
3
2c, Ar ) p-CF3-C6H4
2c, Ar ) p-CF3-C6H4
2b, Ar ) Ph
3
5
5
2b, Ar ) Ph
(ArTe)2 (0.5 eq)
5
2c, Ar ) p-CF3-C6H4
10
a
A: ethylene glycol, 250 °C; B: water, 180 °C.
Some time ago we reported that O-allylated â-hydroxy-
alkyl aryl tellurides were induced to undergo intramo-
lecular group-transfer cyclization by photolysis in reflux-
ing benzene in the presence of hexabutylditin (eq 1).12
In the present paper, we report a microwave-assisted
version of this reaction which, as compared to the original
procedure, is improved in several ways.
in our group.12 Thus, epoxides were regioselectively ring-
opened with arenetellurolates in very good yields. The
resulting alcohols 1 were then allylated using allyl
bromide/NaH in THF (Table 1).
Group-transfer cyclization of compounds 2 was tried
at various temperatures in solvents suitable for micro-
wave heating (2-propanol at 200 °C, NMP at 250 °C,
diethylene glycol dimethyl ether at 250 °C, ethylene
glycol at 250 °C, water at 180 °C). It was found that short
time (<5 min) microwave irradiation under an atmo-
sphere of air in ethylene glycol at 250 °C afforded group
transfer cyclization products in yields similar to those
obtained previously by photolysis in refluxing benzene
in the presence of 40 mol % hexabutylditin.
â-Allyloxyalkyl aryl tellurides 2 were synthesized in
two steps according to a protocol previously developed
Initially, the influence of Te-aryl substituents in cy-
clohexene oxide-derived compounds 2 was examined
(Table 2). The 4-methoxyphenyl, phenyl, and p-(trifluo-
romethyl)phenyl analogues, when reacted until the start-
ing material was consumed, gave approximately the same
yields (65, 69, and 67%, respectively) of group-transfer
cyclization products (Table 2, entries 1, 2, and 4). It was
noted, though, that compound 3a was more sensitive to
air-oxidation than the other analogues. Longer heating
(5 min) at 250 °C seemed to lower the yield (Table 2,
entry 5). This is probably due to decomposition of the
group-transfer product. A striking difference in reactivity
between secondary-alkyl aryl tellurides 2b and 2c was
(8) (a) Crich, D.; Chen, C.; Hwang, J .-T.; Yuan, H.; Papadatos, A.;
Walter, R. I. J . Am. Chem. Soc. 1994, 116, 8937. (b) Yamago, S.; Iida,
K.; Yoshida, J . J . Am. Chem. Soc. 2002, 124, 2874. (c) Yamago, S.;
Iida, K.; Yoshida J . J . Am. Chem. Soc. 2002, 124, 13666. (d) Goto, A.;
Kwak, Y.; Fukuda, T.; Yamago, S.; Iida, K.; Nakajiama, M.; Yoshida,
J . J . Am. Chem. Soc. 2003, 125, 8720. (e) Yamago, S.; Iida, K.;
Nakajiama, M.; Yoshida, J . Macromolecules 2003, 36, 3793.
(9) (a) Miyazoe, H.; Yamago, S.; Yoshida, J . Angew. Chem., Int. Ed.
2000, 39, 3669. (b) Yamago, S.; Miyazoe, H.; Sawazaki, T.; Goto, R.;
Yoshida, J . Tetrahedron Lett. 2000, 41, 7517. (c) Yamago, S.; Miyazoe,
H.; Goto, R.; Hashidume, M.; Sawazaki, T.; Yoshida, J . J . Am. Chem.
Soc. 2001, 123, 3697. (d) Yamago, S.; Miyazoe, H.; Nakayama, T.;
Miyoshi, M.; Yoshida, J . Angew. Chem., Int. Ed. 2003, 42, 117.
(10) Yamago, S.; Hashidume. M.; Yoshida, J . Tetrahedron 2002, 58,
6805.
(11) Lucas, M. A.; Schiesser, C. H. J . Org. Chem. 1996, 61, 5754.
(12) Engman, L.; Gupta, V. J . Org. Chem. 1997, 62, 157.
5144 J . Org. Chem., Vol. 69, No. 15, 2004

TABLE 3. Micr ow a ve-Assisted Gr ou p -Tr a n sfer Rea ction s of P r im a r y-Alk yl Ar yl Tellu r id es
product, isolated yield (%),
entry
2-allyloxyalkyl aryl telluride
Ar
conditionsa
reaction time (min)
cis/trans ratio
1
2
3
4
2d , R ) Bn
Ph
Ph
B
A
A
A
10
6
10
6
3d , <10, 1/2.4
3d , 74, 1/1.8
3e, 60, 1/1.8
3f, 63, 1/1.5
2d , R ) Bn
2e, R ) Bn
2f, R ) PhOCH2
p-CF3-C6H4
Ph
a
A: ethylene glycol, 250 °C; B: water, 180 °C.
observed when the reaction was attempted in water at
180 °C. Even after a prolonged reaction time (10 min)
cyclization of telluride 2c failed to go to completion. When
telluride 2b was heated at 180 °C, the reaction was
complete in 5 min and a 72% yield of product 3b was
isolated. With the hope to increase group-transfer yields,
the corresponding diaryl ditelluride (0.5 equiv) was added
to some of the reaction mixtures. As seen from Table 3
(entries 3 and 7), the additive did not cause any signifi-
cant improvement in yields. Hexabutyldistannane was
also tested as an additive. It caused a drop in product
yields and increased reaction times.
We were also interested to see if primary-alkyl aryl
tellurides could be induced by microwaves to undergo
group transfer (Table 3). Heating at 180 °C for 10 min
in water did not cause cyclization of telluride 2d to go to
completion. However, when the same reaction was per-
formed at elevated temperature (250 °C) in ethylene
glycol, it was complete in 6 min and a 74% yield of the
desired group-transfer product 3d was isolated. Telluride
2e with an electron-withdrawing aryl group was more
reluctant to undergo group transfer. The isolated yield
of compound 3e was 60% (Table 3, entry 3). As a final
example of microwave-assisted formation of tetrahydro-
furan derivatives from primary-alkyl phenyl tellurides,
compound 3f was prepared in 63% yield.
was determined by gNOESY-experiments. Exo/endo
ratios were in the range of 1/1.1-1/1.3 and cis/trans ratios
in the range of 1/1.1-1/1.8. Thus, as compared with tin-
promoted, light-induced group transfer in refluxing ben-
zene,12 selectivity is significantly reduced. The pre-
dominant formation of exo and trans isomers, respec-
tively, is in accord with the Beckwith-Houk model for
ring-closure of 5-hexenyl radicals assuming a chairlike
transition state.13
Although group transfer of organoselenium compounds
is known to proceed slower than those of the correspond-
ing iodine and phenyltelluro analogues, a substantial
number of inter- and intramolecular carboselenation
reactions have been described in the literature.14 The key
to success in these reactions seems related to the radical
stability of the organic moiety attached to the PhSe
groupsat least one and often two stabilizing groups need
to be present.
Spurred by the above results with organotelluriums,
we also attempted some microwave-assisted group-
transfer reactions of related organoselenium compounds.
Compound 5, the selenium analogue of compound 2b,
failed to react even after 20 min of microwave heating
at 250 °C in ethylene glycol. This was also true for the
derivative carrying an electron releasing dimethylamino
group para to selenium.
To demonstrate that the chemistry developed is not
restricted only to heterocycle-construction, alcohol 1g was
group-transfer cyclized to afford compound 4 in 58% yield
as a 1/1.1 mixture of cis and trans isomers (eq 2).
On the other hand, group-transfer cyclization of
benzylic selenide 6 was complete in 5 min, affording
tetrahydrofuran 7 (cis/trans ) 1/2.1) in 75% yield along
(13) (a) Beckwith, A. L. J .; Easton, C. J .; Serelis, A. K. J . Chem.
Soc., Chem. Commun. 1980, 482. (b) Beckwith, A. L. J .; Lawrence, T.;
Serelis, A. K. J . Chem. Soc., Chem. Commun. 1980, 484. (c) Beckwith,
A. L. J . Tetrahedron 1981, 37, 3073. (d) Beckwith, A. L. J .; Schiesser,
C. H. Tetrahedron 1985, 41, 3925. (e) Spellmeyer, D. C.; Houk, K. N.
J . Org. Chem. 1987, 52, 959.
(14) (a) Byers, J . H.; Lane, G. C. Tetrahedron Lett. 1990, 31, 5697.
(b) Byers, J . H.; Harper, B. C. Tetrahedron Lett. 1992, 33, 6953. (c)
Byers, J . H.; Lane, G. C. J . Org. Chem. 1993, 58, 3355. (d) Curran, D.
P.; Geib, S. J .; Kuo, L. H. Tetrahedron Lett. 1994, 35, 6235. (e) Curran,
D. P.; Eichenberger, E.; Collis, M.; Roepel, M. G.; Thoma, G. J . Am.
Chem. Soc. 1994, 116, 4279. (f) Byers, J . H.; Whitehead, C. C.; Duff,
M. E. Tetrahedron Lett. 1996, 37, 2743. (g) Back, T. G.; Gladstone, P.
L.; Parvez, M. J . Org. Chem. 1996, 61, 3806. (h) Renaud, P.; Abazi, S.
Synthesis 1996, 253. (i) Ryu, I.; Muraoka, H.; Kambe, N.; Komatsu,
M.; Sonoda, N. J . Org. Chem. 1996, 61, 6396. (j) Abazi, S.; Rapado, L.
P.; Shenk, K.; Renaud, P. Eur. J . Org. Chem. 1999, 477. (k) Yang, D.;
Gao, Q.; Lee, O.-Y. Org. Lett. 2002, 4, 1239.
Based on general knowledge of radical stability and
our results with primary-alkyl- and secondary-alkyl aryl
tellurides, one can predict that tertiary-alkyl aryl tel-
lurides would be the most reactive substrates for group-
transfer cyclization. Unfortunately, the chemistry devel-
oped (Table 1) failed to produce the desired organotel-
lurium radical precursors (1,1-dimethyloxirane was only
ring-opened from the sterically least hindered side and
ring-opened tetramethyloxirane could not be O-allylated).
Group-transfer cyclization products 3 were always
formed as mixtures of exo/endo (Table 2) or cis/trans
(Table 3) isomers. The stereochemistry of the products
J . Org. Chem, Vol. 69, No. 15, 2004 5145

SCHEME 1
viously only be performed in the presence of toxic tin
mediators using traditional methodologyscould now be
induced to occur without additives in environmentally
benign solvents such as water. We foresee that other
types of group-transfer reactions could be facilitated in
a similar way by microwave heating. The only drawback
we have experienced so far in the new methodology is a
loss in diastereoselectivity. This could be accounted for
by the higher than normal (up to 250 °C) temperatures
required in the microwave-assisted reactions.
with 13% of cyclized but hydrodeselenated compound 8
(Scheme 1). When the reaction was carried out in the
presence of 0.5 equiv of diphenyl diselenide, a 91% yield
of compound 7 was isolated together with only 4% of the
byproduct 8. However, attempts to extend the group-
transfer cyclization to R-phenylseleno esters and nitriles
carrying a suitably positioned allyloxy group elsewhere
in the molecule were met with failure.
Ack n ow led gm en t. The Swedish Research Council
is gratefully acknowledged for financial support. We
thank Dr. Vijay Gupta, Personal Chemistry, for as-
sistance in carrying out some of the microwave-assisted
reactions.
In conclusion, we have demonstrated that group trans-
fer chemistry can be substantially improved if performed
in a microwave cavity. Not only does microwave heating
cause a reduction in reaction time from a few hours to a
few minutes. Group-transfer cyclization of primary- and
secondary-alkyl aryl telluridessreactions that could pre-
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures, characterization data and copies of 13C NMR spectra.
This material is available free of charge via the Internet at
http://pubs.acs.org.
J O040155F
5146 J . Org. Chem., Vol. 69, No. 15, 2004